PROJECT SUMMARY/ABSTRACT The candidate, who has a strong background in pediatric nursing and public health, seeks to become an independent researcher in adolescent health with a focus on the influences of the gut microbiota (the microbes in the intestine) on adolescent depressive symptoms. Adolescent depression is a worldwide phenomenon, with 3% to 5% of adolescents diagnosed with depression. The prevalence of adolescents with depressive symptoms is even higher, estimated at 7% to 28%, so it is crucial to identify the associated risk factors. The gut microbiota may be involved in mechanisms underlying the modulation of adolescent depressive symptoms. This proposal seeks to elucidate the processes of the gut-brain axis, including the mediating role of the immune pathway. The K01 Mentored Research Scientist Development Award will provide the necessary support and training to the candidate to establish a program of research that aspires to promote adolescent health by reducing risk factors for adolescent depressive symptoms. The proposed study will examine an understudied risk factor, the disruption of the gut microbiota. Support and training through the K01 will aid in accomplishing several specific aims: Aim 1 - characterize the gut microbiota of adolescents, Aim 2 - determine whether severity of depressive symptoms is associated with the diversity of gut microbiota composition, Aim 3 - determine if severity of depressive symptoms is associated with lower levels of beneficial bacteria and higher levels of pathogenic bacteria, and Aim 4 - determine whether inflammatory cytokines mediate the relationship between depressive symptoms and levels of beneficial or pathogenic bacteria. The proposed mentored research plan includes individual mentorship, specialized training, and coursework to: 1) design and conduct clinical studies aimed at examining biological risk factors of depressive symptoms, and 2) learn and apply specialized bioinformatics methods to analyze and interpret the gut microbiota. Dr. Leung will manage and conduct a cross-sectional study from project design to completion with a multi-disciplinary group of mentors at the University of California, San Francisco. Dr. Sandra Weiss, who has extensive experience with research studies focusing on adolescent health, biomarkers and depression, will provide overall direction and mentorship. Dr. Susan Lynch will provide mentorship in microbiota collection and analysis. Lastly, Dr. Mark Rubinstein will provide additional training in recruiting, tracking and maintaining adolescent participants. The proposed career development activities and research will provide the knowledge, skills, and experience that will culminate in Dr. Leung?s successful application for a R01 award to independently conduct a longitudinal study to further examine the gut microbiome, the genetic material of the microbes that inhabit the gut community, and immune pathways associated with adolescent depressive symptoms.